The main applications of this invention are in developing improved methods for Cancer Imaging and Cancer Treatment. One out of every four people in the US will die from cancer. There is tremendous interest in developing improved methods of cancer detection and therapy because the earlier the cancer is detected and treated the better the chances of success. Early research on targeting tumors used antibodies obtained from immunized animals. Subsequent studies have been almost exclusively devoted to developing monoclonal antibodies against tumors.
Much of the research has utilized monoclonal antibodies produced by murine hybridomas. There is however a problem when murine monoclonal antibodies are injected into cancer patients. There is a risk that the patient may develop an immune response against the “foreign” protein making further treatment ineffective. In order to avoid this problem there is intensive research into developing methods to “humanize” the monoclonal antibodies by substituting parts of the mouse antibody with human components or by developing fully human monoclonal antibodies.
This invention describes an alternative method of targeting tumors using human antibodies obtained from patients with autoimmune disease. The autoantibodies are not directed against tumor specific antigens and/or tumor associated antigens, but instead are directed against normal intracellular components that are found extracellularly within the necrotic areas often found in tumors.
Many tumors have areas of necrosis and these necrotic areas contain elevated levels of intracellular material released from dead or dying cells. This includes nuclear materials such as the nuclear membrane, nucleoproteins, DNA, histones etc. and cytoplasmic components such as mitochondria, ribosomes and soluble cytoplasmic proteins.
Patients with certain types of autoimmune disorders often produce autoantibodies directed against intracellular components. For example, patients with Systemic Lupus Erythematosus (SLE) have autoantibodies directed against nuclear antigens such as anti-deoxyribonucleoprotein (DNP) antibodies, or anti-Sm antibodies, or anti-DNA antibodies, while patients with Mixed Connective Tissue Disease (MCTD) have antibodies directed against extractable nuclear antigen (ENA). These and other autoantibodies to intracellular components can be used as “carriers” by labeling them with various imaging and therapeutic compounds. For example, antinuclear antibodies labeled with radionuclides or therapeutic drugs will bind to the expressed nuclear material found in necrotic areas of tumors. In contrast, normal healthy tissues do not have necrotic areas and will therefore not be targeted by the autoimmune antibodies.
The novelty of this invention is based on the process of using a blood product (autoantibodies) obtained from patients with autoimmune disease to develop pharmaceutical products for the detection and treatment of cancer.
This invention differs from all previous methods of using human antibodies to treat or prevent various diseases in that in those prior instances the human antibodies that were used were “protective” antibodies obtained from immunized healthy donors and used to protect the recipient from developing the same disease. For example, rhoGAM is an antibody against rhesus factor obtained from immunized donors and used to treat the pregnant mother in order to prevent rhesus disease in the fetus. Another example is the immune globulin preparation obtained from donors who had antibodies to smallpox and used prophylaticly to treat individuals who had been exposed to smallpox infection.
In contrast to the above examples, this invention describes the use of naturally occurring “pathogenic” autoantibodies obtained from individuals with one type of disease (i.e. autoimmune disease) to prepare pharmaceutical products that can be utilized to treat a completely unrelated type of disease (i.e. cancer).
A further benefit of this invention is that these are human autoantibodies and are therefore non-immunogenic to the cancer patient. They can be used repeatedly as “carriers” for cancer imaging and therapy compounds without provoking an immune response in the patient.